Recyclable metathesis catalysts

ABSTRACT

Highly active, recoverable and recyclable transition metal-based metathesis catalysts and their organometallic complexes including dendrimeric complexes are disclosed, including a Ru complex bearing a 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene and styrenyl ether ligand. The heterocyclic ligand significantly enhances the catalytic activity, and the styrenyl ether allows for the easy recovery of the Ru complex. Derivatized catalysts capable of being immobilized on substrate surfaces are also disclosed. The present catalysts can be used to catalyze ring-closing metathesis (RCM), ring-opening (ROM) and cross metatheses (CM) reactions, and promote the efficient formation of various trisubstituted olefins at ambient temperature in high yield.

RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.09/925,555, filed on Aug. 9, 2001 which claims the benefit of U.S.Provisional Application No. 60/264,361 filed on Jan. 26, 2001 and U.S.Provisional Application No. 60/224,305 filed on Aug. 10, 2000.

GOVERNMENT SUPPORT

This invention was supported by a grant from the National ScienceFoundation. The government has certain rights in this invention.

BACKGROUND OF THE INVENTION

Metal-catalyzed olefin metathesis reactions serve as a springboard forthe development of a range of regioselective and stereoselectiveprocesses. These processes are important steps in the chemical synthesisof complex organic compounds and polymers. In particular, thesereactions often are crucial steps in medicinal chemistry for smallmolecule synthesis. Organo-metallic catalysts, particularly transitionmetal complexes based on osmium, ruthenium or tungsten, are used in manysuch organic transformation reactions.

The synthesis and catalytic activity of ruthenium-based complexes whichcan efficiently catalyze ring-opening metathesis (ROM) and ring-closingmetathesis (RCM) of dienes that contain terminal olefins has beenreported for example, by Kingsbury, J. S.; Harrity, J. P. A.;Bonitatebus, P. J.; Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 791-799;Harrity, J. P. A.; Visser, M. S.; Gleason, J. D.; Hoveyda, A. H. J. Am.Chem. Soc. 1997, 119, 1488-1489; and Harrity, J. P. A.; La, D. S.;Cefalo, D. R.; Visser, M. S.; Hoveyda, A. H. J. Am. Chem. Soc. 1998,120, 2343-2351. Because of the risk of metal contamination of theresulting product, and due to the cost of organometallic catalysts,recovery and reuse of such catalysts is important. Kingsbury, et al.showed that an organometallic ruthenium-based catalyst could berecovered from the reaction mixture by silica gel chromatography in highyield and reused in subsequent C—C bond forming reactions. Kingsbury etal., supra. However, there are several shortcomings in the prior artrecyclable metathesis catalyst, including that it is useful mostly forsubstrates that contain terminal alkenes. In certain cases, due toco-elution, isolation of the catalyst from the substrate is problematic.

SUMMARY OF THE INVENTION

The present invention comprises highly active and recyclable transitionmetal-based metathesis catalysts, methods of making such catalysts andtheir use in metathesis reactions. The catalysts of the presentinvention are organometallic complexes of a transition metal comprisingan organic ligand that permits recovery of the catalyst metal from thereaction mixture. The organometallic complexes of the invention can bein monomeric, polymeric and dendritic forms that are capable ofpromoting various forms of metathesis reactions in a highly efficientmanner, and can be efficiently recovered from the reaction mixtures andreused; they are therefore, recyclable. Unlike prior recoverabletransition metal-based complexes, the catalysts of the present inventioneffect the efficient formation of trisubstituted alkenes andtetrasubstituted olefins through catalytic metathesis processes. Thepolymeric and dendritic catalysts of the invention offer the addedadvantage that they are more readily insoluble. The present catalystsare extremely active (can be used to prepare tri- and tetra-substitutedolefins), can be readily recovered and reused and leave little or notrace of toxic metal contamination within the product.

In one aspect, the invention comprises a composition comprising amonomeric catalyst having the following Formula I:

wherein:

M is a transition metal;

X comprises oxygen (O), sulfur (S), nitrogen (N) or phosphorus (P);

R comprises an alkyl, alkenyl, alkynyl, aryl, alkoxy, alkenyloxy,alkynyloxy, aryloxy, alkoxy carbonyl, alkylamino, alkylthio,alkylsulfonyl, alkylsulfinyl; each optionally substituted with an alkyl,halogen, alkoxy, aryl or heteroaryl moiety;

R₁ and R₂ each comprise, or together comprise, an electron withdrawinganionic ligand;

a, b, c, and d each comprises H, a halogen atom or an alkyl, alkenyl,alkynyl, aryl, alkoxy, alkenyloxy, alkynyloxy, aryloxy, alkoxycarbonyl,alkylamino, alkylthio, alkylsulfunyl; alkylsulfinyl; each optionallysubstituted with an alkyl, halogen, aryl or heteroaryl moiety; and

Y comprises an electron-donating heterocyclic carbene ligand.

In a preferred embodiment, M is ruthenium, X is O, R is a lower alkylgroup (e.g., C₁-C₁₂), R₁ and R₂ are halogen atoms (which may beidentical or different but preferably are identical), a, b, c and d eachcomprises hydrogen or a lower alkyl group (e.g., C₁-C₁₂), and Ycomprises a 4,5-dihydroimidazol-2-ylidene carbene ligand ring structureor a phosphine moiety. In a more preferred embodiment, M is ruthenium, Xis O, R is isopropyl, R₁ and R₂ are chlorine atoms (Cl), a, b, c and deach comprises hydrogen, and Y comprises a heterocyclic ring structurehaving the following Formula II:

wherein R₃ and R₄ comprise he same or different aromatic ring moieties.In a currently preferred embodiment, R₃ and R₄ both comprise2,4,6-trimethylphenyl(mesityl) moieties.

In another aspect, the invention comprises dendritic catalyst structurehaving the following Formula III:

wherein R₅, R₆, R₇ and R₈ each comprises the following Formula IV:

wherein:

-   -   M comprises a transition metal;    -   X comprises O, S, N or P;    -   R comprises an alkyl, alkenyl, alkynyl, aryl, alkoxy,        alkenyloxy, alkynyloxy, aryloxy, alkoxy carbonyl, alkylamino,        alkylthio, alkylsulfunyl, alkylsulfinyl; each optionally        submitted with an alkyl, halogen, aryl or heteroaryl moiety;

R₁ and R₂ each comprises, or together comprise, an electron withdrawinggroup; and Z comprises Y or a phosphine group.

In a preferred embodiment, M is Ru, X is O, R is a lower alkyl group(e.g., C₁-C₁₂), R₁ and R₂ are halogen atoms (which may be identical ordifferent but preferably are identical), and Z comprises a phosphinemoiety having the formula P(Cy)₃, wherein Cy comprises an aliphatic ringstructure, preferably cyclohexyl or cyclopentyl. In a currentlypreferred embodiment, M is Ru, X is O, R is isopropyl, R₁ and R₂ each isa chlorine atom (Cl), and Z is P(cyclohexyl)₃.

In another preferred embodiment, M is Ru, X is O, R is a lower alkylgroup (e.g., C₁-C₁₂), R₁ and R₂ are halogen atoms and Z comprises a ringstructure having Formula II wherein R₃ and R₄ comprise the same ordifferent aromatic ring moieties. In a currently preferred embodiment, Mis Ru, X is O, R is isopropyl, R₁ and R₂ are chlorine atoms (Cl) and Zcomprises a ring structure having Formula II wherein R₃ and R₄ bothcomprise a 2,4,6-trimethyl phenyl(mesityl) moiety.

The present invention provides stable, readily recoverable transitionmetal-based metathesis catalysts with high catalytic activity. Thecatalysts may be used free in the reaction mixture or may be immobilizedon a solid phase. In another aspect of the invention, the monomericcatalysts of Formula I are immobilized on a solid phase. In a preferredembodiment, the catalysts of the invention are immobilized on solidphases such as, for example, metals, glass, polymers, ceramics, organicpolymer beads, inorganic sol-gels or other inert substances, withoutimpairing their ability to catalyze various forms of metathesisreactions in a highly efficient manner. In a currently preferredembodiment, the solid phase is an inorganic sol gel such as, forexample, a glass monolithic gel. In addition, the invention comprisesthe design and synthesis of various chiral versions of the presentmonomeric and dendritic complexes and their application to asymmetriccatalytic metathesis.

Immobilization of catalysts of the invention to an inorganic monolithicgel provides the following advantages over immobilization of suchcatalysts on conventional solid phases such as organic polymer beads:(1) overcomes limitations of organic polymer beads such as variableswelling and shrinking in different media, often resulting in reductionof catalytic activity (2) precludes the addition of significant volumesof solvents needed for recovery of beads bound to the catalyst, anecessity that seriously limits the utility of recoverable surfaceimmobilized catalysts, thereby detracting from the practicality of suchan approach and rendering it more costly and environmentally lessfriendly. (3) The high porosity characteristic of inorganic gelstranslates to a substantially large interfacial surface area (typically300-1000 m²/g), rendering such materials ideal for immobilization ofcatalysts of the invention. (4) Gelation occurs after a sol is cast intoa mold; it is, therefore, possible to tailor the gel samples to adesired shape or even function.

In another preferred embodiment, the surface immobilized catalysts ofthe present invention is an integral part of the reaction apparatusitself, thus obviating the need for a filtration step to recover thecatalyst after completion of metathesis processes. Processes of thepresent invention are, therefore, rendered operationally simple from thestandpoint of both execution and work-up.

The recyclable catalysts of the present invention are substantially moreactive than prior art recyclable metathesis catalysts. The transitionmetal-based monomers and dendrimers of the present invention are easilycharacterizable and serve as homogeneous metathesis catalysts that arehighly active and allow for significantly more facile catalyst recoverycompared to prior art catalysts.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows two prior art ruthenium catalysts: (1) is a recoverablecomplex of ruthenium with an isopropoxystyrene and a phosphine moiety,and (2) is a benzylidene catalyst.

FIG. 2 shows an ORTEP diagram of Cl₂Ru(═CH-o-OiPrC₆H₄)(4,5-dihydrolMES)(Formula 5). Thermal ellipsoids are drawn at 30% probability level, andselected bond distances and angles are shown in Table 1.

FIG. 3 shows the transition metal catalysts (1, 2) and organometalliccompound 3 comprising an active metal complex.

FIG. 4 shows surface immobilized catalysts of the invention coupled to asolid phase (represented by a spherical solid substrate) via differenttypes of linkers.

DETAILED DESCRIPTION OF THE INVENTION

The present invention comprises a novel class of recoverable andrecyclable organometallic metathesis catalysts. The term “recoverable”as used herein means that the catalyst can be recovered or retrievedfrom the reaction mixture once the reaction is complete. The term“recyclable” means that the recovered catalyst can be reused insubsequent metathesis reactions after recovery from the previousreaction(s).

The catalysts of the present invention comprise novel monomericcatalysts having the structure of Formula I, and dendritic catalystshaving the structure of Formula III. The present monomeric and dendriticcatalysts are recoverable and recyclable, and can efficiently catalyze avariety of olefin metathesis reactions, including ring-openingmetathesis (ROM), ring-closing metathesis (RCM), cross-metathesis (CM),ring-opening polymerization metathesis (ROMP), and acyclic dienemetathesis (ADMET). The catalysts of the present invention can be usedin most metathesis reactions under appropriate conditions. Those skilledin the art would be able to empirically determine the amount of catalystand optimal conditions of the reaction. For example, the monomeric anddendritic catalysts of the present invention can be used in mostreactions at levels of from about 1.0 mol % to about 5.0 mol %.

The present catalysts can be recovered from the reaction mixture by anytechnique suitable for recovering or separating organometalliccomplexes, including chromatography or filtration. For example, themonomeric or dendritic catalysts may be separated form the reactionmixture by silica gel chromatography. If the catalyst is attached to asolid phase, as described below, then the catalyst can be recovered byseparating the solid phase from the reaction mixture by simplefiltration.

Monomeric complexes. In one aspect, the present invention providesmonomeric catalysts having the structure shown as Formula I. Monomericcatalysts having Formula I can be prepared according to the proceduresshown in Equation 1 below, in Examples 1-10, or via other syntheticroutes that would be readily ascertainable by those skilled in the art.

The structure shown as Formula 5 in Equation 1 below comprises acurrently preferred embodiment of the present invention.

Synthesis of Formula 5. The catalyst of Formula 5 was synthesized andcharacterized, and its reactivity and recyclability were determined. Itwas determined that the saturated imidazolin-2-ylidene and unsaturatedimidazol-2-ylidene carbene ligands accelerated the metathetic activityof Ru-based complexes. As depicted in Equation 1, treatment of compound3 with 2.5 equivalents CuCl and 0.97 equivalents of compound 4 in CH₂Cl₂at 40° C. delivers the Formula 5 catalyst within 1 hour; the Formula 5catalyst was isolated as an air stable green solid in quantitative(>98%) yield after silica gel chromatography (mp=178-181° C. dec).

Single-crystal X-ray structure analysis of a Formula 5 catalyst is shownin FIG. 2; (IMES=1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene). Thecrystal structure analysis confirms the structural assignment shown inFormula 5. Selected bond lengths and angles for Formula 5 are providedin Table 1. The overall geometry around the transition metal center andmost of the bond angles and bond lengths in Formula 5 are analogous totheir related values in the complex of Formula 6 (shown in Scheme 1).

Comparison of the ¹H NMR spectra of prior art compound 1 (shown inFIG. 1) and the Formula 5 catalyst show some of the differentialstructural attributes of these complexes. As illustrated in Scheme 1,there are two distinct chemical shift changes in the 400 MHz ¹H NMRspectra of Formula 5 catalyst and compound 1. One variation is observedat the iso-Pr methine proton and another at the carbene CH (H_(α)). Inboth instances, the protons for the imidazolin-2-ylidene system inFormula 5 are more shielded. These differences may be attributed tohigher electron density at the transition metal center of Formula 5,caused by the stronger electron donation by the heterocyclic ligand(compared to PCy₃ (Cy is an aliphatic cycloalkyl moiety, preferablycyclohexyl). The weaker electron donation by the oxygen ligand to the Rucenter in Formula 5 may be manifested by the more upfield appearance ofthe isopropyl methine proton (5.28 vs 4.90 ppm).

TABLE 1 Selected Bond Lengths and Angles for Cl₂Ru(═CH-o-OiPrC₆H₄)(4,5-dihydrolMES) (Formula 5) Bond lengths (Å) Ru(1)—C(1)1.828 (5) Ru(1)—Cl(1) 2.328 (12) Ru(1)—C(2) 1.981 (5) Ru(1)—Cl(2) 2.340(12) Ru(1)-0(1) 2.261 (3) C(2)—N(1) 1.351 (6) C(2)—N(2) 1.350 (6) Bondangles (deg) C(1)—Ru(1)-0(1) 79.3 (17) 0(1)-Ru(1)—Cl(1) 86.9 (9)C(1)—Ru(1)—C(2) 101.5 (14) 0(1)-Ru(1)—Cl(2) 85.3 (9) C(2)—Ru(1)-0(1)176.2 (14) C(2)—Ru(1)—Cl(1) 96.6 (12) C(1)—Ru(1)—Cl(1) 100.2 (15)C(2)—Ru(1)—C(2) 90.9 (12) C(1)—Ru(1)—Cl(2) 100.1 (15) Cl(1)—Ru(1)—Cl(2)156.5 (5) N(1)—C(2)—N(2) 106.9 (4)

Catalytic Activity and Recovery of Formula 5 catalyst. The data in Table2 below illustrate that the Formula 5 catalyst is an effective catalystfor RCM of dienes. In this reaction, hetero- and carbocyclic compoundsbearing trisubstituted alkenes were obtained from the correspondingprecursor dienes in the presence of 5 mol % catalyst at ambienttemperature within 10 min. to 2 h. As shown in entries 1 and 2 of Table2, both 1,1-disubstituted (7) and trisubstituted olefins (9) may beutilized in the synthesis of trisubstituted cyclic alkenes. Thecatalytic RCM in entries 3-4 indicate that trisubstituted allylicalcohols (12) and acetates (14) can be accessed in the presence of 5 mol% 5 within 2 h. The Ru catalyst of Formula 5 is recovered with highefficiency (95% and >98% yield, respectively). The prior art catalyst 1is significantly less efficient in promoting the above transformations.As an example, treatment of structure 11 with 5 mol % 1 (22° C., CH₂Cl₂)leads to only 15% conversion after 2 h (as judged by 400 MHz ¹H NMR).

Two important points in connection to the above data are important:

(1) In all instances, the catalyst is recovered, along with the desiredcyclic product in high yield after simple silica gel chromatography.Moreover, addition of 2 equivalents of styrene ether 4 (relative to thecatalyst) to a solution of a transformation promoted by thenon-recyclable 3 at the end of the reaction time, leads to the isolationof the recyclable catalyst 5. As an example: Treatment of diene carbinol11 is treated with 5 mol % 3 (CH₂Cl₂, 22° C., 1 h), followed by theaddition of 10 mol % 4 and addition stirring for 1 h, leads to theformation of 12 and 5 in 98% and 82% yields, respectively (after silicagel chromatography).

(2) Catalyst loading lower than 5 mol % is sufficient. As exemplified bythe reaction in entry 2, catalytic RCM can readily proceed to completionwith only 1 mol % Formula 5 catalyst. As another example, catalytic RCMof 7 occurs within 10 mm at 22° C. in the presence of 1 mol % of 5 toafford 8 in 73% isolated yield (>98% cony); recovered 5 is obtained in92% yield after chromatography.

As the reaction in entry 5 of Table 2 indicates, tetra-substitutedolefins can also be obtained through catalytic RCM promoted by thecatalyst of Formula 5.

TABLE 2 Ring-Closing Metathesis of Acyclic Dienes by Ru Complex 5^(a)product catalyst entry substrate product time conv (%) yield (%)^(b)recovery (%)^(b) 1

10 min >98 82 98 2

20 min >98 87 98 3

2 h >98 75 95 4

1.5 h >98 82 >98 5

44 h 42 38 81 6

30 min 70 65 60 ^(a)Conditions: 5 mol % 5 for entries 1 and 3-6, 1 mol %5 for entry 2, 22° C., CH₂Cl₂ (entries 1-4); 24 h at 22° C. and 20 h at40° C., CH₂Cl₂ for entry 5; toluene, 80° C. for entry 6. ^(b)Isolatedyields after silica gel chromatography.

In this instance, the Ru catalyst is recovered in >80% yield. Whentoluene is used as the solvent in the catalytic RCM of compound 17,tetrasubstituted alkene 18 is formed in 65% isolated yield within 30minutes (70% conversion).

The catalysts used the above-described transformations may be retrievedfrom the reaction mixture, e.g., using silica gel chromatography, andthen may be used in subsequent metathesis reactions with equalefficiency and without recrystallization. For example, the catalystrecovered from the reaction in entry 1 of Table 2 was reused in the samereaction to afford the desired product 8 in 71% isolated yield (10minutes, 22° C.). The Formula 5 catalyst was again recovered in 98%yield after chromatography.

As shown by the representative transformations in Scheme 2, Formula 5also is an efficient catalyst in ROM/RCM and ROM/CM processes. Bothtransformations were completed within 1 hour, with >98% conversion.

Scheme 3 shows the release/return mechanism by which the presentmonomeric catalysts function as metathesis catalysts. As shown therein,a diene substrate probably first reacts with the initial Ru complex toremove the transition metal from the styrene ligand and “release” thestyrene ether 4. Upon consumption of the diene, the active Ru-carbenereacts with the previously occupied styrenyl ether to cause reformationor “return” of the initial complex.

Dendritic complexes. In another aspect, the present invention providesdendritic catalysts having the structure shown as Formula III. Dendriticcatalysts having Formula III can be prepared according the proceduresdescribed below, in Examples 11-16, or via other synthetic routes thatwould be readily ascertainable to these skilled in the art.

The structures shown as Formulae 30 and 31 below comprise currentlypreferred embodiments of the present invention.

Dendritic complexes, due to their different polarity compared to themonomeric species, generally can be more easily separated from reactionproducts. With dendrimers, it is possible to gauge more rigorously theefficiency with which the active metal-carbene leaves the ligation siteand returns to the catalyst macromolecule. In addition both the releaseof the metal center from the styrenyl ligand (initiation) and the returnof the active metal to the initial site (recovery), which is shown inScheme 3 above, are more efficient with the more accessible and exposedterminal sites within the dendrimer structure.

Synthesis of Ru-Containing Dendrimers. In a currently preferredembodiment, the dendrimers are tetraalkylsilyl systems. Scheme 4 belowshows a synthetic scheme for synthesizing a preferred Ru-containingdendrimer (Formula 30).

a. anhydrous HCl, i-PrOH, >87%, b, 2 equiv NaH, 2 equiv i-PrI, DMF, THF,89%. c. 1.1 equiv Br₂, HOAc, CH₂Cl₂, 98%. d. 1.1 equiv Bu₃SnCHCH₂, 3 mol% Pd(PPh₃)₄, 2 mol % BHT, tol, 110° C., 4 h, >98%. g. 4.3 equivHMe₂SiCl, 5 mol % H₂PtCl₆ in THF, 3 h. h. 4.2 equiv CH₂CHCH₂MgBr, Et₂O,22° C., 3 h, >90% overall for two steps. i. 5.1 equiv 9-BBN, THF, 22°C., 17 H; NaOH, H₂O₂, EtOH, THF, 22° C., 6 h, 96%. J. 4.9 equiv EDC.HCl,4.5 equiv 26, 0.6 equiv DMAP, 22° C., 3 h, 63%. k. 4.3 equiv 2, 4.6equiv CuCl, CH₂Cl₂, 22° C., 3 h, 83%.

The key features of the synthesis shown in Scheme 4 include theattachment of the requisite vinyl group through a pallidium(Pd)-catalyzed Stille coupling (→26) and preparation of the dendrimerbackbone by a platinum (Pt)-catalyzedhydrosilation/alkylation/hydroboration sequence (27→28→29). Coupling of29 with four equiv 26, followed by incorporation of the Ru centerthrough treatment with 2 in the presence of CuCl affords the desired 30as an air stable brown solid (mp=92-98° C. dec.).

Another preferred Ru-containing dendrimer, Formula 31, can be preparedas an air stable dark green solid by the same sequence of reactions asshown in Scheme 4, except that the last step involves treatment of thevacant dendritic structure with 4.3 equiv 3 and 4.6 equiv CuCl in CH₂Cl₂for 10 mm (55% yield; mp=114-117° C. dec).

Catalytic RCM, ROM and CM Promoted by Dendritic Catalysts of Formulas 30and 31. Table 3 below illustrates the use of the present dendriticcatalysts in a RCM reaction. As shown in Table 3, treatment of diene 32with 1.25 mol % of 30 (5 mol % Ru) leads to efficient and catalytic RCM.The desired product (33) is first isolated in 99% yield by silica gelchromatography through elution with CH₂Cl₂ subsequent wash of the silicawith Et₂O leads to the isolation of the dendritic catalyst (>98% massbalance). Recovered 30 was analyzed by 400 MHz ¹H NMR spectroscopy; theresulting spectrum indicated that 13% of the styrenyl ligands werevacant (approximately 13% Ru loss).

TABLE 3 Utility of Dendritic Catalyst Formula 30 in Catalyzing RCMproduct yield^(a) Ru content^(b) Cycle (%) (%) 1 99 87 2 91 76{graveover ( )} 3 96 72 4 89 64 5 92 48 6 87 41 ^(a)Isolated yields aftersilica gel chromatography. ^(b)Determined by analysis of the 400 MHz ¹HNMR of the purified reaction mixture of dendrimer after silica gelpurification (devoid of other Ru- containing impurities).

As illustrated in Table 3, repeated use of Formula 30 as a catalystresults in complete conversion of 32 to 33 and isolation of the desiredproduct in >86% isolated yield. These data thus illustrate thatdendrimer 30 is effective in promoting the catalytic RCM of terminaldienes in a highly efficient manner, and can be easily recovered bysimple silica gel filtration and reused repeatedly in subsequentreactions. In addition, after repeated use, the partially depleteddendrimer complex can be easily re-metalated upon treatment with theappropriate equivalents of 3 and CuCl in CH₂Cl₂. The dendritic complexremains active even after nearly 50% of the Ru content has been depleted(see cycle 6 in Table 3). This level of reactivity may be attributed, atleast partially, to the fact that 30 (similar to monomeric catalysts 1and 5) releases a highly active mono-phosphine Ru complex into thesolution. In the absence of a second equivalent of PCy₃ that canre-coordinate to Ru and retard its catalytic activity (which is the casewhen 2 or 3 are used as catalysts), and since styrene ethers probably donot kinetically re-associate with Ru as efficiently as PCy₃, even asmall amount of Ru release can lead to substantial amounts of metathesisactivity.

Metal crossover experiments were carried out as depicted in Scheme 5.Treatment of compound 4 with dendritic Ru complex of Formula 30 resultsin little or no metal crossover (<2% 1 formed by 400 MHz ¹H NMRanalysis). The amount of Ru bound to the dendritic vs monomeric ligandsis readily determined by the chemical shift difference in the ¹H NMRspectra of the corresponding carbene CH (Ru═C(H)). When diene substrate32 is treated with 1.25 mol % fully loaded 30 and 4 mol % 4, RCM product33 is obtained within 15 mm. However, recovered 30 bears 42% less Ru,compared to 13% metal reduction when the reaction is carried out in theabsence of 4 (see Table 3, cycle 1). In addition, ˜30% of uncomplexed 4is isolated after the reaction; the remainder of the monomeric styrenylalkoxide is recovered as monomeric Ru complex 1. These observationsindicate that the Ru metal, after reacting with the diene substrate andleaving the dendrimer, can be trapped again by a styrenyl alkoxide.Thus, in the absence of compound 4, the catalytically active Rumonophosphine would likely return to a styrene unit within the dendriticstructure.

Dendrimer 31 exhibits catalytic activity higher than that observed for30. Unlike 1 or 30, but similar to 5, dendritic 31 efficiently promotesthe formation of trisubstituted allylic alcohol 12 (Scheme 4); inaddition to the desired product (78%), the dendrimer is recovered aftersilica gel chromatography quantitatively with 8% loss in Ru loading(judged by analysis of 400 MHz ¹H NMR). Moreover, as shown in Equation(5), similar to 5, dendrimer 31 effectively catalyzes tandem ROM/RCM of19 and the formation of 20 (94%). However, in contrast to thecorresponding monomer 5, dendrimer 31 can be easily separated from 20and recovered in 90% yield (8% Ru loss). The transformation in Scheme 6indicates that 31 effectively promotes catalytic ROM/CM reactions aswell, and as before, it can be recovered readily and in good yield (>98%trans olefins in 22 and 34, as judged by 400 MHz ¹H NMR analysis). Thus,dendritic catalyst 31 retains the high activity of monomeric 5 andprovides the valuable practical advantage of being readily separablefrom metathesis products.

Similar to monomeric 5, lower loadings of 31 are sufficient forefficient catalytic metathesis. As an example, when triene 7 is treatedwith 0.25 mol % 31 (CH₂Cl₂, 22° C.) for 10 min, RCM adduct 8 is formedwith >98% cony. In addition to dihydrofuran 8, isolated in 84% yield,recovered 31 is obtained in 88% yield after silica gel chromatography(22% Ru loss).

Immobilization of the Catalysts on a Solid Phase. The present catalystscan be attached to or immobilized on a solid support for use inmetathesis reactions. Solid phases which can be used include, forexample, metals (including magnetic media), glass, polymers, ceramics orother inert substances that will not affect the reaction. The solidphase may be in any form useful for carrying out the particularreaction, including particles, beads, rods, plates, fibers, filters,etc. Methods for attaching organometallic catalysts to solid supportsand using them in metathesis reactions are known in the art. One methodfor attaching the preferred monomeric catalyst of the present inventionto a polymer substrate is described in Example 19.

The catalysts of the present invention can be immobilized with retentionof all the ligand environment characteristics responsible for its highactivity. In one embodiment, the immobilized catalyst is immobilized onthe solid support in a manner such that the support is a catalystcarrier. In this embodiment, the metathesis substrate releases theactive metal carbene from the polymer, the complex promotes severalcycles in solution, and is again trapped by the support so that it canbe easily retrieved and reused. In other words, the present immobilizedcatalyst systems combine the benefits of heterogeneous catalysis(recyclability) and homogeneous catalysis (high turnover).

In a preferred embodiment of the invention, the transition metalcatalysts are immobilized on solid phase surfaces such as, for example,metals, glass, polymers, ceramics, organic polymer beads, inorganicsol-gels and other inert substances, without impairing their ability tocatalyze various forms of metathesis reactions in a highly efficientmanner. In a currently preferred embodiment, the solid phase is aninorganic sol gel such as, for example, a glass monolithic gel.

The surface immobilization of the catalysts to solid phase substratesinvolves a preliminary step wherein the catalysts are chemically reactedwith an organic coupling agent to provide adducts that are capable ofchemically bonding to said solid phase substrates. In a preferredembodiment, the said adduct contains a silyl functionality that enablessurface immobilization on solid phase substrates via chemical bonding ofthe silyl group to the said substrates. In a most preferred embodimentthe catalysts of the invention are coupled to the organic linker andfunctionalized with a silane-containing moiety in a single step. Surfaceimmobilization of the said silane modified compounds onto solid phasesubstrates is accomplished in-situ by subsequent addition of saidsubstrate into the reaction vessel. Preferred coupling agents arenorbornene derivatives that are capable of reacting with catalysts ofthe invention, and further capable of reacting with organo-silane agentsto provide silyl-functionalized derivatives that may be used in surfaceimmobilization reactions. Preferred solid phase substrates include thosecapable of chemically reacting with the silyl moiety. In a mostpreferred embodiment, the solid phase substrate is a porous glassmonolith having preferably an average pore size of about 200 Å. Morespecifically, as shown in Scheme 7, a ring-opening reaction combinedwith cross metathesis of anti-norbornenol ester 35 in with 1.0equivalent each of organometallic complex 3 andallylchlorodimethylsilane (0.05 M CH₂Cl₂, 22° C.) proceeds to >98%conversion in <1 h to give adduct 36 (analyzed by 400 MHz ¹H NMR).Surface immobilization of adduct 36 is accomplished by adding apre-weighed batch of vacuum-dried sol-gel monoliths such as, forexample, glass monolithic gel with about 200 Å pore size to the reactionmixture, followed by stirring for 96 h at 40° C. After extensive washingwith CH₂Cl₂ and drying in vacuo, bright green glass pellets of surfaceimmobilized catalyst 37 are recovered.

In other preferred embodiments, surface immobilized catalysts 38 and 39shown in FIG. 4 are obtained in an analogous fashion from thecorresponding norbornene substrates. Surface immobilized catalysts 37,38 and 39 were evaluated for catalytic activity, recovery andrecyclability.

All surface immobilized catalysts of the present invention show goodactivity in catalyzing metathesis reactions. Table 4 shows efficiency ofimmobilized catalysts 37, 38 and 39 carried through iterative rounds ofring-closing metathesis (RCM) of acrylic amide 40 to yield 41. Thecatalyst 1o:

that accompany functionalization of the gel surface. Relative reactionrates of three catalysts were assessed by stopping the reactionprematurely during the third round of RCM, at a point where TLC analysisstill showed the presence of a small amount of starting material.Spectroscopic analysis of the (400 MHz ¹H NMR) unpurified reactionmixture (97-100% conversion, Round 3, Table 4) indicates that reactionefficiency of all three catalysts tested are equivalent.

TABLE 4 Utility of Immobilized Catalysts in catalyzing RCM

Catalyst Round 1 (3 h) Round 2 (3 h) Round 3 (2 h) Round 4 (3 h) MetalLoss 37 >98% conv, 99% >98% conv, 100% 97% conv, 100% >98% conv, 99% 1.8mg (25%) 38 >98% conv, 100% >98% conv, 100% 97% conv, 99% >98% conv,100% 1.9 mg (20%) 39 >98% conv, 99% >98% conv, 99% 99% conv, 100% >98%conv, 100% 1.6 mg (22%)

The surface immobilized catalysts of the present invention provide thefollowing advantages over non-immobilized catalysts 1 and 2 and 3 (FIG.3).

(1) In contrast to reactions run with 5 mol % non-immobilized catalysts1 and 2, the proton NMR spectra of the unpurified reaction mixtures inevery case consists of >98% pure cyclo-olefin (analyzed by 400 MHz ¹HNMR); no catalyst or byproduct thereof is detected). Concentration ofthe reaction mixtures consistently deliver the cyclo-olefins as anoff-white solids in >98% yield. These materials meet the acceptancecriteria as defined by CH combustion analysis without need forpurification.

(2) No post reaction filtration step is required for product isolationand catalyst recovery. The reaction mixture is removed by pipetting,decantation or pumping, following which the solid surface (for example,inorganic gel pellets such as glass) with the immobilized catalyst iswashed with CH₂Cl₂, prior to addition of fresh substrate for asubsequent metathesis reaction.

(3) After four consecutive rounds of RCM utilizing surface immobilizedcatalysts with different organic linker types, the respective gelpellets after thorough drying in vacuo and subsequent weighing yieldedmass differences that are highly reproducible, indicating a net metalloss of between 20 to 25% over the four reaction cycles. Despite thissignificant drop in Ru catalyst loading relative to the initial values,the catalytic activities of the recovered, recycled gel pellets remainhigh. Absence of cross-contamination of reaction products by surfaceimmobilized catalysts of the present invention may be demonstrated byusing the same samples for the ring-opening metathesis (ROM) of7-anti-norbornenol in the presence of a variety of donor olefins,including highly electron-rich olefins such as vinylferrocene. As shownin Table 5, productive metathesis for three additional rounds ofnorbornenol 42 occurred in <1 h to yield ring-opened compound 43. TheRu-containing impurities, as well as the product of the previous RCMreaction 41 could not be detected by NMR spectroscopy (400 MHz ¹H NMRanalysis) of the corresponding unpurified reaction product mixtures.

TABLE 5 Efficiency of Recycled Catalysts in catalyzing ROCM

R = Ph R = n-hexyl R-Ferrocene Catalyst Rounds 5 (40 min) Round 5 (40min) Round 7 (40 min) 37 >98% conv >98% conv >98 conv 38 >98% conv >98%conv >98 conv 39 >98% conv >98% conv >98 conv

In addition to attaching the catalyst to a substrate such as an organicpolymer bead that necessitates an additional filtration step to isolatethe product from catalyst, the catalysts of the invention may beimmobilized on the surface of a reaction vessel. In a preferredembodiment, the catalyst metal complex is immobilized to an integralpart of the reaction apparatus itself, for example, a glass round-bottomreaction flask, a magnetic stir bar, or other component used to carryout the reaction. Catalysts of the present invention may also beattached to highly porous glass monoliths, which can be synthesized andmanipulated from readily available materials.

Preferably, the linker moiety used to bind the metal complex to thesolid support should be chemically inert under the reaction conditionsand form a non-labile link between the metal complex and support. In oneembodiment, as shown in Scheme 7, the present catalysts are immobilizedusing a procedure that allows incorporation of both the linker and theactive metal complex in a single step. Subsequent diffusion of thecatalyst and linker into the pores of a sol gel material, for example,results in a substitution reaction involving the labile Si—Cl bond withfree hydroxyl groups on the glass surface, thereby immobilizing thecatalyst to the glass surface.

As shown in Example 19, ring-opening cross metathesis (0.10 mmol scale)of a strained olefin using the catalyst synthesized according to Example4 (shown as Formula 3 in Equation 1 above) proceeded to >98% conversion.In this reaction, a catalyst of the present invention was immobilized ona single 50 mg sol gel monolith. After extensive washing and drying invacuo, a bright green glass pellet was recovered which showed goodactivity in the RCM of the terminal diene (0.10 mmol scale). Theimmobilized catalyst was carried through three iterative rounds ofmetathesis.

The following Examples are provided to illustrate the present invention,and are not intended to be limiting in any way.

Examples

General. Infrared (IR) spectra were recorded on a Perkin-Elmer 781spectrophotometer, λmax in cm⁻¹. Bands are characterized as broad (br),strong (s), medium (m), and weak (w). ¹H NMR spectra were recorded onVarian Unity 300 (300 MHz), Gemini 2000 (400 MHz), or INOVA 500 (500MHz) spectrometers. Chemical shifts are reported in ppm fromtetramethylsilane with the solvent resonance as the internal standard(CDCI₃): δ7.26 ppm; CD₃CN: δ 1.94 ppm). Data are reported as follows:chemical shift, multiplicity (s=singlet, d=doublet, t=triplet, br=broad,m multiplet), coupling constants (Hz), integration, and assignment. ¹³CNMR spectra were recorded on Varian Unity 300 (75 MHz), Gemini 2000 (100MHz), or INOVA 500 (125 MHz) spectrometers with complete protondecoupling. Chemical shifts are reported in ppm from tetramethylsilanewith the solvent as the internal reference (CDCl₃: 77.00 ppm; CD₃CN:1.19 ppm). ³¹P NMR spectra were recorded on a Varian Gemini 2000 (162MHz) spectrometer with complete proton decoupling. The chemical shiftsof the phosphorus resonances were determined relative to phosphoric acidas an external standard (H₃PO₄: δ0.0 ppm).

All reactions were carried out under an atmosphere of dry Ar in oven-(135° C.) and flame-dried glassware with standard Schlenk or vacuum-linetechniques. In most instances, solid organometallic compounds werepurified and recovered in air and later stored in a drybox under anatmosphere of argon. (PCy₃)Cl₂RuCHPh (Formula 2) was prepared accordingto literature procedures.³⁰ (4,5-dihydrolMES)(PCy₃)Cl₂Ru═CHPh (Formula3) and its requisite starting materials were prepared by a modificationof the published method³¹(see below for further details).2-isopropoxystyrene was prepared by alkylation and Wittig olefination.All other materials were obtained from commercial sources and purifiedbefore use. Tetrahydrofuran, diethyl ether, benzene, and toluene weredistilled from sodium metal/benzophenone ketyl. Dichloromethane,pentane, hexanes, 2-propanol, triethylamine, and ethanol were distilledfrom calcium hydride under Ar. Methanol was distilled over Mg under Ar.2,4,6-trimethylaniline was vacuum distilled. Triethyl orthoformate(Aldrich) was distilled from MgSO₄ under reduced pressure.3-(4-Hydroxyphenyl)-propionic acid (Aldrich) was recrystallized fromwater. 2-Iodopropane (Aldrich) was distilled from MgSO₄ under argon.Dimethylformamide (Fisher) was stored over 4A molecular sieves prior touse. Tributyl(vinyl)tin (Aldrich) was vacuum distilled from MgSO₄.Allylmagnesium bromide was freshly prepared from distilled allyl bromide(Aldrich) and Mg turnings (Strem) and titrated before use. Silicontetrachloride (Strem) was distilled under argon. Chlorodimethylsilane(Aldrich) was distilled under argon. 9-Borabicyclo[3.3.1]nonane (9-BBN)was freshly prepared from distilled 1,5-cyclooctadiene (Aldrich),borane-dimethylsulfide complex (Aldrich), and anhydrous dimethoxyethane(Aldrich, distilled from sodium metal/benzophenone ketyl).³²4-Dimethylaminopyridine (DMAP) (Aldrich) was recrystallized fromanhydrous toluene. The following materials were purchased fromcommercial sources and used as received: glyoxal (40% wt. sole in water)(Aldrich), sodium cyanoborohydride (Aldrich), bromocresol green(Fisher), ammonium tetrafluoroborate (Aldrich), potassium tert-butoxide(Strem), copper(I) chloride (Strem), anhydrous HCl (Aldrich), sodiumhydride (Aldrich), bromine (Aldrich), acetic acid (Fisher), sodiumthiosulfate (Aldrich), 2,6-di-tert-butyl-4-methylphenol (Aldrich),tetrakis(triphenylphosphine)palladium (0) (Strem), activated carbon(Aldrich), chloroplatinic acid hexahydrate (Speier's catalyst) (Strem),platinum-divinyltetramethylsiloxane complex in xylene (Karstedt'scatalyst) (Geleste), hydrogen peroxide (30% wt. soln in water)(Aldrich), citric acid (Aldrich), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) (Advanced Chemtech).

All silica gel column chromatography was driven with compressed air andperformed with silica gel 60 (230-400 mesh; pH (10% suspension) 6.5-7;surface area 500 m²/g; pore volume 0.75 ml/g) obtained from TSI ChemicalCo. (Cambridge, Mass.). Similar to the original monomer 1, dendriticcatalyst 30 forms a dark brown solution in organic solvents. Incontrast, the more active catalysts bearing the 4,5-dihydrolMES ligandform bright green-colored organic solutions. The purification of theabove complexes can be easily monitored visually since they appear asdark brown or green-colored bands on the column. Dendritic complexes 30and 31 are significantly more polar than the corresponding monomers.Following a metathesis reaction mediated by 30 or 31, isolation of bothproduct and catalyst typically involved simply a filtration of the crudemixture through a silica gel plug in 100% CH₂Cl₂ followed by a column“flush” in 100% Et₂O (TLC Rf of 30 and 31 <1.0 in CH₂Cl₂).

Example 1

Synthesis of ((2,4,6-Trimethylphenyl)NCH)₂. Glyoxal (3.73 mL of a 40%weight solution in water, 32.5 mmol) was dissolved in 325 mL ofreagent-grade methanol in a 500 mL flask. 2,4,6-Trimethylaniline (8.25mL, 58.8 mmol, 1.81 equiv) was added dropwise to this solution bysyringe. The mixture was stirred for 12 h at 22° C. as a bright yellowprecipitate slowly formed. The mixture was diluted with CH₂Cl₂,dissolving the solid. The resulting yellow solution was dried overMgSO₄, filtered, and concentrated to a yellow-orange solid residue. Theunpurified product was recrystallized from anhydrous methanol (for every10 g, 850-900 mL of MeOH was required for complete dissolution atreflux). After slow cooling to 22 EC followed by subsequent storage ofthe sample at −20° C. for 12 h, long canary yellow crystals formed. Theproduct was recovered by vacuum filtration, washed with pentane, anddried under high vacuum (7.40 g, 25.3 mmol, 86%). IR (NaCl): 3005 (m),2946 (s), 2916 (s), 2854 (m), 2725 (w), 1617 (s), 1595 (w), 1476 (m),1438 (w), 1374 (m), 1265 (m), 1202 (s), 1141(m), 1031 (w), 850 (s), 780(m), 739 (s), 705 (w), 609 (w). ¹H NMR (400 MHz, CDCl₃): 8.12 (s, 2H,NCH), 6.93 (s, 4H, aromatic CH), 2.31 (s, 6H, mesitylp-CH₃), 2.18 (s,12H, mesityl o-CH₃). ¹³C NMR (100 MHz, CDCl₃): δ3.31, 147.29, 134.13,128.86, 126.44, 20.83, 18.28. HRMS Calcd for C₂₀H₂₃N₂: 292.1861 (M−H)⁺.Found: 291.1862. Anal. Calcd for C₂₀H₂₄N₂: C, 82.15; H, 8.27. Found: C,81.99; H, 8.12.

Example 2

Synthesis of ((2,4,6-Trimethylphenyl)NHCH₂)₂. The bis(imine)((2,4,6-trimethylphenyl)NCH) (7.30 g, 25.0 mmol) was suspended in 250 mLof MeOH in a 500 mL round-bottom flask. Several crystals of bromocresolgreen were added as a pH indicator and the mixture was cooled to 0° C.NaCNBH₃ (10.0 g, 159 mmol, 6.4 equiv) was added to the reaction mixturein one portion as a solid. Vigorous bubbling was observed and thereaction mixture turned a deep blue-green color (alkaline pH). After 10mm concentrated HCl was added dropwise to the mixture, restoring itsoriginal yellow color. Additional reduction slowly occurred, causing themixture to again become basic. The acidification process was repeated(typically two more times) until the yellow color persisted. Thereaction mixture was warmed to 22° C. and stirred for 1 h. A solution of2 M KOH was added dropwise until the mixture was weakly alkaline(pH=8-9). The mixture was then diluted with water (300 mL), transferredto a separatory fume, and washed three times with Et₂O (500 mL). Thecombined organic layers were washed with 800 mL of saturated solution ofsodium chloride, dried over MgSO₄, filtered, and concentrated into ayellow oil. Silica gel chromatography (TLC Rf=0.32 in 4:1 pentane:Et₂O)afforded the product as a colorless oil (7.13 g, 24.1 mmol, 96%). IR(NaCl): 3367 (br), 2996 (s), 2916 (s), 2854 (s), 2729 (w), 1612 (w),1485 (s), 1446 (s), 1373 (m), 1344 (w), 1228 (s), 1207 (m), 1154 (m),1110 (m), 1062 (w), 1030 (m), 1012 (m), 853 (s), 822 (w), 801 (w), 738(m), 563 (m). ¹H NMR (400 MHz, CDCl₃):δ 6.85 (s, 4H, aromatic CH), 3.30(br, 21-1, NH), 3.17 (s, 4H, NCH₂CH₂N), 2.30 (s, 12H, mesityl o-CH₃),2.25 (s, 6H, mesitylp-CH₃). ¹³C NMR (100 MHz, CDCl₃): δ 143.24, 131.35,129.65, 129.38, 49.19, 20.60, 18.50. HRMS Calcd for C₂₀H₂₈N₂: 296.2252Found: 296.2258. Anal. Calcd for C₂₀H₂₈N₂: C, 81.03; H, 9.52. Found: C,81.28; H, 9.41.

Example 3

Synthesis of 1,3-Dimesitylimidazolinium tetrafluoroborate. A 25 mLround-bottom flask was charged with ((2,4,6-trimethylphenyl)NHCH₂)₂(7.81 g, 26.4 mmol) and ammonium tetrafluoroborate (2.77 g, 26.4 mmol,1.0 equiv). Triethylorthoformate (4.39 mL, 26.4 mmol, 1.0 equiv) wasadded by syringe. The flask was equipped with a reflux condenser andsubmerged into a preheated oil bath at 120° C. The mixture was refluxedfor 3 h and cooled to 22° C. A tan-colored solid precipitated, leaving acloudy suspension. This mixture was recrystallized from hot anhydrousethanol. The resulting bright white crystals of product were recoveredby vacuum filtration, washed with pentane, and dried under high vacuum(5.62 g, 14.3 mmol, 54%). Additional product could be obtained byfurther recrystallization of the mother liquor. IR (NaCl): 3091 (w),2979 (br), 2941 (br), 1633 (s), 1487 (w), 1459 (w), 1393 (w), 1313 (w),1269 (m), 1214 (w), 1092 (m), 1054 (s), 1036 (s), 965 (w), 880 (w), 852(m). ¹H NMR (400 MHz, CD₃CN): δ 8.14 (s, 1H, NCHN), 7.08 (s, 4H,aromatic CH), 4.43 (s, 4H, NCH₂CH₂N), 2.37 (s, 12H, mesityl o-CH₃), 2.32(s, 6H, mesitylp-CH₃). ¹³C NMR (100 MHz, CD₃CN): δ 160.41 (d,^(J)NC=10.3 Hz), 141.54, 136.50, 131.36, 130.61, 52.21, 21.16, 17.92.HRMS Calcd for C₂₁H₂₇N₂: 307.2174 (cation only). Found: 307.2175. Anal.Calcd for C₂₁H₂₇BF₄N₂: C, 63.97; H, 6.90. Found: C, 63.79; H, 6.85.

Example 4

Synthesis of (4,5-dihydrolMES)(PCy₃)Cl₂Ru═CHPh (formula 3). The ligandsalt 1,3-dimesitylimidazolinium tetrafluoroborate (2.94 g, 7.46 mmol,1.2 equiv) was suspended in 50 mL of THF in a 250 mL round-bottom flask.This mixture was then treated with a solution of potassium tert-butoxide(840 mg, 7.49 mmol, 1.2 equiv) in 50 mL of THF via cannula at 22° C.This mixture was immediately cannula transferred (20 mL THF used asrinse) to a second vessel containing a solution of (PCy₃)Cl₂Ru═CHPh (2)(5.01 g, 6.09 mmol, 1.0 equiv) in 100 mL of benzene (additional stirringof the ligand salt mixture at 22° C. prior to exposure to the Ru-carbeneoften resulted in incomplete conversion to the desired product). Theresulting mixture was refluxed at 80° C. for 30 min. and then cooled to22° C. All manipulations from this point forward were carried out in airwith reagent-grade solvents. The solvents were removed at reducedpressure, leaving a red-brown solid residue. The crude residue wasdissolved in a minimal volume of 9:1 hexanes: Et₂O and loaded onto awide plug of silica gel. Elution with the same solvent system slowlyremoved a pink-red band of the desired product from the column.Concentration of the product fractions in vacuo removed the more polarand volatile Et₂O and resulted in spontaneous precipitation of thecatalyst from hexanes as a cranberry red, microcrystalline solid (3.78g, 4.45 mmol, 73%). These crystals were dried under high vacuum. IR(NaCl): 3057 (m), 3039 (m), 3015 (m), 2927 (s), 2850 (s), 1608 (w), 1479(s), 1446 (s), 1421 (s), 1380 (m), 1328 (w), 1266 (s), 1243 (m), 1205(w), 1174 (m), 1129 (w), 1036 (w), 1005 (m), 909 (m), 849 (m), 737 (s),703 (m), 687 (m), 624 (w), 578 (w). ¹H NMR (300 MHz, CDCl₃): δ 19.13(s,1H, Ru=CHAr), 7.35 (dd, J=7.8, 7.0 Hz, 2H, aromatic CH), 7.09 (m, 3H,aromatic CH), 7.01 (s, 4H, mesityl aromatic CH), 3.98 (s, 4H, N(CH₂)₂N),2.80-0.70 (m, 33H, P(C₆H₁₁)₃), 2.31 (s, 12H, mesityl o-CH₃), 1.90 (s,6H, mesitylp-CH₃). ¹³C NMR (75 MHz, CDCl₃): δ 293.40, 220.29 (d,^(J)CN=76.2 Hz), 151.16, 151.11, 138.27, 137.49, 137.08, 135.06, 129.77,127.78, 51.64 (d, ^(J)CN =71.9 Hz), 31.30 (d, ^(J)PC=15.6 Hz), 27.68 (d,=9.8 Hz), 26.07, 21.09, 20.86, 19.88. ³¹P NMR (162 MHz, CDCl₃): δ 161.90(s, PCy₃). Anal. Calcd for C₄₆H₆₅Cl₂N₂PRu: C, 65.08; H, 7.72. Found: C,65.18; H, 7.71.

Example 5

Synthesis of (4,5-dihydrolMES)Cl₂Ru═CH-o-O-i-PrC₆H₄ (formula 5).(4,5-dihydrolMES)(PCy₃)Cl₂Ru═CHPh (formula 3) (895 mg, 1.05 mmol, 1.03equiv) and CÜCI (261 mg, 2.64 mmol, 2.59 equiv) were weighed into a 100mL round-bottom flask in a glove box and dissolved in 20 mL of CH₂Cl₂.2-isopropoxystyrene (4) (166 mg, 1.02 mmol, 1.0 equiv) was cannulatedinto the resulting deep red solution in 20 mL of CH₂Cl₂ at 22° C. Theflask was equipped with a condenser and stirred at reflux for 1 h. Fromthis point forth, all manipulations were carried out in air withreagent-grade solvents. The reaction mixture was concentrated in vacuoto a dark brown solid residue. The crude material was dissolved in aminimal volume of 2:1 pentane: CH₂Cl₂ and loaded onto a plug of silicagel. Elution with 2:1 pentane: CH₂Cl₂ and then 1:1 pentane: CH₂Cl₂removed a bright green band from the column. The column was then washedsuccessively with straight CH₂Cl₂ and Et₂O (light green/yellow bandselute). These three fractions were pooled and concentrated to a darkgreen solid. This material was passed through a second silica gel plugin 1:1 hexanes:CH₂Cl₂ (bright green band elutes). Subjection to reducedpressure removed the more volatile CH₂Cl₂ from the product solution andresulted in spontaneous precipitation of the catalyst from hexanes as abright green crystalline solid; drying under high vacuum afforded 635 mg(1.01 mmol, 99%) of the desired product. IR (NaCl): 2922 (br), 2853 (m),1730 (w), 1606 (w), 1589 (m), 1575 (w), 1478 (s), 1452 (s), 1420 (s),1397 (m), 1384 (m), 1295 (m), 1263 (s), 1217 (m), 1160 (w), 1113 (s),1098 (w), 1035 (w), 938 (m), 852 (w), 801 (w), 746 (m), 737 (m), 580(m). ¹H NMR (400 MHz, CDCl₃): δ 16.56 (s, 1H, Ru═CHAr), 7.48 (m, 1H,aromatic CH), 7.07 (s, 4H, mesityl aromatic CH), 6.93 (dd, J=7.4, 1.6Hz, 1H, aromatic CH), 6.85 (dd, J=7.4, 7.0 Hz, 1H, aromatic CH), 6.79(d, J=8.6 Hz, 1H, aromatic CH), 4.90 (septet, J=6.3 Hz, 1H,(CH₃)₂CHOAr), 4.18 (s, 4H, N(CH₂)₂N), 2.48 (s, 12H, mesityl o-CH₃), 2.40(s, 6H, mesityl p-CH₃), 1.27 (d, J=5.9 Hz, 6H, (CH₃)₂CHOAr). ¹³C NMR(100 MHz, CDCl₃): 6296.83 (q, J=61.5 Hz), 211.13, 152.04, 145.13 (d,Joc=3.9 Hz), 145.09, 138.61, 129.39 (d, ^(J)NC=3.9 Hz), 129.35, 129.17,122.56, 122.11, 112.75, 74.86 (d, ^(J)oc=10.7 Hz), 51.42, 30.86, 25.93,21.08. HRMS Calcd for C₃₁H₃₈Cl₂N₂O⁹⁹Ru: 623.1421 Found: 623.1411. Anal.Calcd for C₃₁H₃₈Cl₂N₂ORu: C, 59.42; H, 6.11; Cl, 11.32; N, 4.47. Found:C, 59.28; H, 6.35; Cl, 11.36; N, 4.12.

Example 6

Synthesis of Isopropyl-1-(p-hydroxyphenyl)propionate. Through a stirringsolution of 3-(4-hydroxyphenyl)propionic acid (24) (5.00 g, 30.1 mmol)in 2-propanol (167 mL, 72.0 equiv) was bubbled anhydrous HCl for 50 mm.The flask was sealed under Ar and stirred for 12 h at 22° C. The solventwas removed under reduced pressure with gentle heating, leaving a thick,colorless oil. Removal of residual 2-propanol under high vacuum at 22°C. resulted in spontaneous precipitation of the desired product as abright white crystalline solid (6.12 g, 29.4 mmol, 98%). IR (NaCI): 3412(br), 3024 (w), 2981 (m), 2930 (w), 2873 (w), 1712 (m), 1613 (s), 1595(m), 1519 (s), 1449 (m), 1377 (s), 1298 (m), 1266 (s), 1225 (s), 1149(m), 1108 (s), 904 (m), 837 (m), 820 (m), 609 (m). ¹H NMR (400 MHz,CDCl₃): δ 7.04 (d, J 8.4 Hz, 2H, aromatic CH), 6.74 (d, J=8.4 Hz, 2H,aromatic CH), 5.80 (s,1H, ArOH), 5.00 (septet, J=6.3 Hz, 1H, (CH₃)₂CHO),2.87 (t, J=7.6 Hz, 2H, CH₂CO₂iPr), 2.57 (t, J=7.6 Hz, 2H, ArCH₂), 1.20(d, J=6.3 Hz, 6H, (CH₃)₂CHO). ¹³C NMR (100 MHz, CDCl₃): δ 172.97,154.04, 132.19, 129.28, 115.19, 68.07 (d, J_(OC)=9.8 Hz), 36.64, 30.23,21.85. HRMS Calcd for C₁₂H₁₆0₃: 208.1099. Found: 208.1099. Anal. Calcdfor C₁₂H₁₆0₃: C, 69.21; H, 7.74. Found: C, 69.43; H, 7.88.

Example 7

Synthesis of Isopropyl-1-(p-isopropoxyphenyl)propionate (25). A solutionof isopropyl-I-(phydroxyphenyl)propionate (0.822 g, 3.95 mmol) in THF(10 mL) was treated via cannula with a suspension of sodium hydride (104mg, 5.92 mmol, 1.1 equiv) in THF (10 mL) at 0° C. After gas evolutionhad subsided, DMF (20 mL) and 2-iodopropane (0.40 mL, 4.0 mmol, 1.0equiv) were syringed into the reaction mixture. The resulting suspensionwas stirred at 22° C. for 6 hours, at which time additional sodiumhydride (71.0 mg, 2.96 mmol. 0.75 equiv) in THF (5 mL) and 2-iodopropane(0.30 mL, 3.0 mmol, 0.75 equiv) were added. This procedure was repeatedif necessary until no starting material could be detected by TLCanalysis (we suspect that competing elimination of the electrophile isresponsible for incomplete product conversions, requiring us toresubject the reaction mixture). The mixture was then diluted with Et₂O(150 mL) and water (200 mL) and transferred to a separatory funnel. Theorganic layer was removed, and the aqueous layer was washed twice withEt₂O (100 mL). The combined organic layers were washed with threevolumes of water to remove residual DMF. The organic solution was thendried over MgSO₄, filtered, and concentrated in vacuo to a pale yellowoil. The product was passed through a short column of silica gel in 7:1hexanes:Et₂O affording 811 mg (3.24 mmol, 82%) of a colorless oil (TLCRf=0.30 in 7:1 hexanes:Et₂O). IR (NaCl): 2978 (m), 2934 (w), 1731 (s),1612 (w), 1510 (s), 1452 (w), 1383 (m), 1295 (w), 1242 (s), 1182 (m),1109 (s), 957 (w), 829 (w). ¹H NMR (400 MHz, CDCl₃): δ 7.09 (d, J=8.6Hz, 2H, aromatic CH), 6.80 (d, J=8.6 Hz, 2H, aromatic CH), 5.00 (septet,J=6.3 Hz, 1H, (CH₃)₂CHO₂C), 4.50 (septet, J=6.3 Hz, 1H, (CH₃)₂CHOAr),2.87 (t, J=7.8 Hz, 2H, CH₂CO₂iPr), 2.55 (t, J=7.8 Hz, 2H, ArCH₂), 1.32(d, J=6.3 Hz, 6H, (CH₃)₂CHOAr), 1.20 (d, J=6.3 Hz, 6H, (CH₃)₂CHO₂C). ¹³CNMR (100 MHz, CDCl₃): δ 172.39, 156.12, 132.43, 129.15, 115.81, 69.86(d, J_(OC)=3.4 Hz), 67.59 (d, J_(OC)=9.8 Hz), 36.59, 30.26, 22.14,21.88. HRMS Calcd for C₁₅H₂₂O₃: 250.1569. Found: 250.1566. Anal. Calcdfor C₁₅H₂₂0₃: C, 71.97; H, 8.86. Found: C, 72.26; H, 9.04.

Example 8

Synthesis of Isopropyl-1-(m-bromo-p-isopropoxyphenyl)propionate. A 50 mLround-bottom flask was charged withisopropyl-1-(p-isopropoxyphenyl)propionate (25) (1.09 g, 4.34 mmol) andCH₂Cl₂ (20 mL, 0.20 M). 10 mL of acetic acid (0.18 mmol) was added tothe solution. Bromine (0.235 mL, 4.56 mmol, 1.05 equiv) was then slowlyadded dropwise via syringe, forming a red-colored solution. Over thecourse of 0.5 h, the solution gradually turned a pale yellow color asthe bromine was consumed. After 1 h the reaction was quenched with 5 mLof saturated sodium thiosulfate. The mixture was diluted with water (200mL) and Et₂O (200 mL) and partitioned in a separatory funnel. Theaqueous layer was washed with 2×150 mL of Et₂O. The combined organiclayers were dried over MgSO₄, filtered, and concentrated to a yellowoil. This material could be purified by vacuum distillation or silicagel chromatography (TLC R_(f)=0.23 in 10:1 hexanes:Et₂O) to deliver theproduct as a colorless oil (1.40 g, 4.25 mmol, 98%). Crucial to thesuccess of this reaction is this use of exactly 1.0-1.1 equiv ofbromine; an excess of the reagent leads to dibrominated adducts. Ifthese impurities are generated, a CH₂Cl₂/pentane solvent system must beused as eluant to effect purification of the desired product on silicagel (TLC R_(f)=0.30 in 3:2 CH₂Cl₂:pentane). The halogenated solvent mixalso promotes a facile separation of the product and the startingmaterial (25) in the event that the reaction does not proceed tocompletion (<1.0 equiv Br₂). IR (NaCl) 2979 (m), 2936 (w), 1729 (s),1604 (w), 1493 (s), 1384 (m), 1373 (m), 1281 (m), 1253 (s), 1240 (m),1180 (m), 1140 (m), 1109 (s), 1046 (w), 954 (m), 812 (w). ¹H NMR (400MHz, CDCl₃): δ 7.38 (d, J=2.2 Hz, 1H, aromatic CH), 7.06 (dd, J=8.4, 2.2Hz, 1H, aromatic CH), 6.83 (d, J=8.4 Hz, 1H, aromatic CH), 4.96 (septet,J=6.2 Hz, 1H, (CH₃)₂CHO₂C), 4.50 (septet, J=6.2 Hz, 1H, (CH₃)₂CHOAr),2.85 (dd, J=7.7, 7.3 Hz, 2H, CH₂CO₂iPr), 2.55 (dd, J=7.7, 7.3 Hz, 2H,ArCH₂), 1.36 (d, J=5.9 Hz, 6H, (CH₃)₂CHOAr), 1.20 (d, J=6.6 Hz, 6H,(CH₃)₂CHO₂C). ¹³C NMR (100 MHz, CDCl₃): δ 172.06, 152.84, 134.36, 133.09(d, J_(OC)=7.3 Hz), 128.03, 115.98, 113.63, 72.34 (d, J_(OC)=3.9 Hz),67.80 (d, J_(OC)=12.2 Hz), 36.29, 29.90, 22.15 (d, J_(OC)2.4 Hz), 21.89(d, J_(OC)3.4 Hz). HRMS Calcd for C₁₅H₂₁BrO₃: 328.0674. Found: 328.0671.Anal. Calcd for C₁₅H₂₁BrO₃: C, 54.72; H, 6.43. Found: C, 54.84; H, 6.43.

Example 9

Synthesis of Isopropyl-1 -(p-isopropoxy-m-vinylphenyl)propionate.Pd(PPh₃)₄ (166 mg, 0.144 mmol, 3 mol %) and2,6-di-tert-butyl-4-methylphenol (1 mg, 0.005 mmol) were weighed into a50 mL pear-shaped flask in a glove box and dissolved in 25 mL of drytoluene. This solution was transferred through a cannula into a neatsample of isopropyl-1-(m-bromo-p-pisopropoxyphenyl)propionate (1.58 g,4.79 mmol) in a 50 mL round-bottom flask. The resulting pale yellowsolution was stirred for 15 mm at 22 EC. Tributyl(vinyl)tin (1.54 mL,5.27 mmol, 1.1 equiv) was then added dropwise to the reaction mixturethrough a syringe. The flask was equipped with a condenser and heated at110° C. for 12 h. As the reaction progressed, a shiny mirror-like filmof Bu₃SnBr salts was gradually deposited on the walls of the flask.After cooling to 22° C., the reaction mixture was passed through a smallplug of celite and activated carbon using Et₂O as the eluant andconcentrated in vacuo to give a yellow oil. Purification by silica gelchromatography (TLC R_(f)=0.27 in 8:1 hexanes:Et₂O) afforded 888 mg of acolorless oil (3.22 mmol, 67%). IR (NaCl): 2978 (s), 2936 (m), 2873 (w),1731 (s), 1627 (w), 1491 (s), 1373 (m), 1246 (s), 1180 (m), 1109 (s),996 (w), 957 (m), 904 (w), 814 (w). ¹H NMR (400 MHz, CDCl₃): δ 7.31 (d,J=2.3 Hz, 1H, aromatic CH), 7.07-6.99 (m, 2H, aromatic CH and ArCHCH₂),6.80 (d, J8.2 Hz, 1H, aromatic CH), 5.71 (dd, J=17.8, 1.6 Hz, 1H,ArCHCH₂), 5.22 (dd, J=11.3, 1.6 Hz, LH, ArCHCH₂), 5.00 (septet, J=6.3Hz, 1H, (CH₃)₂CHO₂C), 4.49 (septet, J=6.3 Hz, 1H, (CH₃)₂CHOAr), 2.88(dd, J=7.8, 7.4 Hz, 2H, CH₂CO₂/Pr), 2.57 (dd, J=8.2, 7.4 Hz, 2H, ArCH₂),1.33 (d, J=6.3 Hz, 6H, (CH₃)₂CHOAr), 1.21 (d, J=6.3 Hz, 6H,(CH₃)₂CHO₂C). ¹³C NMR (100 MHz, CDCl₃): δ 172.37, 153.50, 132.52,131.81, 128.38, 127.67, 126.21 (d, J_(OC) 5.4 Hz), 114.42, 113.76 (d,J_(OC)=8.3 Hz), 70.01 (d J_(OC), 3.4 Hz), 67.64 (d, J_(OC)11.2 Hz),36.58, 30.40, 22.28, 21.93. HRMS Calcd for C₁₇H₂₄0₃: 276.1725. Found:276.1716. Anal. Calcd for C₁₇H₂₄0₃: C, 73.88; H, 8.75. Found: C, 73.71;H, 8.73.

Example 10

Synthesis of I-(p-isopropoxy-m-vinylphenyl)propionic acid (26). A 100 mLround-bottom flask was charged withisopropyl-1-(p-isopropoxy-m-vinylphenyl)propionate (462 mg, 1.67 mmol)and 66.8 mL of 1 M KOH (66.8 mmol, 40 equiv). The reaction vessel wasequipped with a condenser and heated at 100° C. for 12 h. The mixturewas then diluted with 100 mL of water, transferred to a 500 mLErlenmeyer flask, and cooled to 0° C. The mixture was neutralized by thedropwise addition of ice-cold 1 M HCl. At a pH of ˜7, 150 mL of Et₂O wasadded. The aqueous layer was acidified further to pH 3-4 with vigorousstirring, resulting in spontaneous precipitation of the product thatimmediately enters the organic phase. The layers were partitioned in aseparatory funnel (an emulsion may form, requiring extended time forphase separation), and the aqueous layer was washed with additional Et₂O(150 mL). The pH of the aqueous layer was then lowered to ˜2 in thepresence of Et₂O. Again, the organic layer was collected and the aqueouslayer was washed. The organic layers were pooled and washed with 500 mLof a saturated solution of sodium chloride. Drying over MgSO₄ andconcentration in vacuo afforded 355 mg (1.52 mmol, 91%) of a lightyellow solid which proved to be >98% pure as judged by ¹H NMRspectroscopy (400 MHz). If necessary, the acid could be further purifiedby silica gel chromatography (TLC R_(f)=0.31 in 3:2 hexanes:Et₂O). It isrecommended that the above procedure be followed with care since theproduct is quite prone to acid-catalyzed polymerization of the styrenemoiety. Rapid, uncontrolled addition of the acid or acidification in theabsence of Et₂O can result in complete loss of the product topolymerization. IR (NaCl):2979 (m), 2935 (w), 2860 (w), 2760 (w), 1686(s), 1600 (s), 1243 (s). ¹H NMR (500 MHz, CDCl₃): δ 11.26 (br, 1H,CO₂H), 7.32 (d, J=2.3 Hz, 1H, aromatic CH), 7.06-7.00 (m, 2H, aromaticCH and ArCHCH₂), 6.81 (d, J=8.5 Hz, 1H, aromatic CH), 5.72 (dd, J=17.8,1.5 Hz, 1H, ArCHCH₂), 5.23 (dd, J=11.0, 1.5 Hz, 1H, ArCHCH2), 4.50(septet, J=6.1 Hz, 1H, (CH₃)₂CHOAr), 2.90 (dd, J=8.0, 7.6 Hz, 2H,CH₂CO₂iPr), 2.67 (dd, J=8.0, 7.6 Hz, 2H, ArCH₂), 1.34 (d, J=6.2 Hz, 6H,(CH₃)₂CHOAr). ¹³C NMR (125 MHz, CDCl₃): δ 178.78, 153.77, 132.13,131.88, 128.40, 127.87, 126.29, 114.48, 113.99, 70.99, 35.80, 29.88,22.19. HRMS Calcd for C₁₄H₁₈0₃: 234.1256. Found: 234.1257. Anal. Calcdfor C₁₄H₁₈0₃: C, 71.77; H, 7.74. Found: C, 71.71; H, 7.68.

Example 11

Synthesis of Tetraallylsilane (27). A 250 mL 2-neck flask equipped witha condenser and addition funnel was charged with freshly preparedallylmagnesium bromide in Et₂O (92.3 mL of a 0.95 M solution, 87.7 mmol,4.1 equiv). SiCl₄ (2.45 mL, 21.4 mmol) was slowly added to the solutionof Grignard reagent through the addition funnel in 20 mL of Et₂O at 22°C. over the course of 1 h. After 12 h of reflux at 35° C., the reactionwas cooled to 0° C. and quenched with 10 mL of a saturated solution ofammonium chloride. The mixture was diluted with water (200 mL) and Et₂O(100 mL) and transferred to a separatory funnel. The organic layer wascollected and the aqueous layer was washed with 2×150 mL of Et₂O. Theorganic layers were dried over MgSO₄, filtered, and concentrated invacuo into a colorless oil. This material was passed through a smallplug of silica in hexanes (TLC R_(f)=0.9 in hexanes) and concentrated.Vacuum distillation afforded 3.33 g (17.3 mmol, 81%) of the product as acolorless oil. IR (NaCl): 3078 (m), 3060 (w), 2996 (w), 2972 (m), 2916(w), 2882 (w), 1630 (s), 1419 (m), 1393 (m), 1195 (m), 1154 (m), 1037(m), 991 (s), 930 (m), 893 (s), 810 (m), 601 (m). ¹H NMR (400 MHz,CDCl₃): δ 5.80 (ddt, J=16.8, 10.2, 8.2 Hz, 4H, CH═CH₂), 4.94-4.87 (m,8H, CH═CH₂), 1.61 (ddd, J=8.2, 1.4, 1.0 Hz, 8H, SiCH₂). ¹³C NMR (100MHz, CDCl₃): δ 134.07, 113.93, 19.03. Anal. Calcd for C₁₂H₂₀Si: C,74.92; H, 10.48. Found: C, 75.01; H, 10.32.

Example 12

Synthesis of Si[(CH₂)₃Si(Me)₂CH═CH_(2]4) (28). A 0.1 M solution ofH₂PtCl₆.6H₂O (Speier's catalyst)³⁴ was freshly prepared in anhydrous2-propanol. The hydrosilylation could also be effected with Karstedt'scatalyst.³⁵ A 25 mL round-bottom flask was charged with the tetraene(27) (762 mg, 3.96 mmol), HMe₂SiCl (2.00 mL, 18.0 mmol, 4.6 equiv), andTHF (0.5 M, 8.0 mL). The platinum catalyst (10.0 mL, 0.010 mmol, 0.0025equiv) was added dropwise by syringe and the colorless solution washeated at reflux (65° C.) for 12 h. After 20 mm of reaction, the mixturehad turned dark green in color. Reaction progress was monitored readilyby thin-layer chromatography; the starting material (TLC R_(f)=0.9 inhexanes) stains bright yellow with KMnO₄. Following the removal ofsolvent and excess silane in vacuo, ¹H NMR analysis (400 MHz) of theunpurified mixture indicated that <5% of the α-substituted product waspresent and that the material was sufficiently pure for the subsequentalkylation step. Thus, the product was dissolved in 20 mL of Et₂O andtransferred by cannula into a solution of freshly preparedallylmagnesium bromide (0.936 M, 17.8 mL, 16.7 mmol, 4.2 equiv). Thereaction was stirred for 12 h at 22° C. and quenched with 10 mL of asaturated solution of ammonium chloride. The mixture was diluted withwater (200 mL) and Et₂O (150 mL) and partitioned in a separatory funnel.The aqueous layer was washed with 2×100 mL of Et₂O. The combined organiclayers were washed with a volume of saturated sodium chloride, driedover MgSO₄, and vacuum filtered through a coarse frit funnel containingcelite. Removal of volatiles gave a crude light orange oil which waspurified by silica gel chromatography (TLC R_(f)=0.63 in hexanes). Theproduct was recovered as a colorless oil (2.11 g, 3.56 mmol, 90%). IR(NaCl): 3077 (w), 2954 (m), 2913 (s), 2876 (m), 1630 (m), 1418 (w), 1250(s), 1153 (m), 1034 (w), 990 (w), 932 (w), 893 (s), 844 (s), 698 (w),629 (w). ¹H NMR (400 MHz, CDCl₃): δ 5.78 (ddt, J=16.8, 10.2, 8.2 Hz, 4H,CH═CH₂), 4.87-4.79 (m, 8H, CH═CH₂), 1.51 (d,J=8.2 Hz, 8H, SiCH₂CH═CH₂),1.32 (m, 8H, SiCH₂CH₂CH₂Si), 0.62-0.53 (m, 16H, SiCH₂CH₂CH₂Si), −0.02(s, 24H, Si(CH₃)₂). ¹³C NMR (100 MHz, CDCl₃): δ 135.21, 112.47, 23.49,19.93, 18.55, 17.54, −3.52. HRMS Calcd for C₃₂H₆₇Si₅: 591.4089 (M−H)+.Found: 591.4072. Anal. Calcd for C₃₂H₆₈Si₅: C, 64.78; H, 11.55. Found:C, 64.98; H, 11.55.

Example 13

Synthesis of Ar(CH₂)₂CO₂(CH₂)₃Si(Me)₂(CH₂)₃SiI₄ (29).Si[(CH₂)₃Si(Me)₂CH═CH₂]₄ (28) (587 mg, 0.989 mmol) was weighed into a 50mL round-bottom flask and dissolved in 10 mL of THF. This solution wastreated by cannula with freshly prepared 9-BBN (527 mg, 4.69 mmol, 4.74equiv) in 10 mL of THF. After 12 h of stirring at 22° C., 10 mL each ofH₂O₂ (30% wt. solution in water), 2 M NaOH, and ethanol were added. Themixture was then allowed to stir an additional 12 h at 22° C. Water (100mL) and Et₂O (100 mL) were added and the organic layer was removed. Theaqueous layer was washed with 2×100 mL of Et₂O. The combined organiclayers were dried over MgSO₄ and filtered. Removal of volatiles gave acrude oil that was purified by silica gel chromatography (TLC R_(f)=0.36in EtOAc). ¹H NMR analysis (400 MHz) indicated that the productcontained minor impurities (including cyclooctadiol) which madecharacterization of the material difficult. Thus, the crude product wascarried directly into the next step. The tetraol was transferred to a 25mL round-bottom flask, dissolved in 15 mL of CH₂Cl₂, and cooled to 0° C.1-(p-isopropoxy-m-vinylphenyl)propionic acid (26) (1.02 g, 4.35 mmol,4.4 equiv), EDC (912 mg, 4.76 mmol, 4.8 equiv), and DMAP (61 mg, 0.50mmol, 0.50 equiv) were then directly added in succession to the mixtureas solids. The resulting mixture was stirred for 4 h and quenched with 2mL of a 10% citric acid solution. Additional water was added (200 mL)and the aqueous layer was washed with 3×100 mL of Et₂O. The combinedorganic layers were washed with 1 volume each of a saturated solution ofsodium chloride and water. Drying over MgSO₄, filtration, andconcentration gave a crude oil which was purified by silica gelchromatography (TLC R_(f) 0.36 in 4:1 hexanes:EtOAc). The desiredtetra(ester) was recovered as a colorless oil (954 mg, 0.623 mmol, 63%).IR (NaCl): 2974 (m), 2951 (m), 2919 (s), 2873 (m), 2855 (m), 1735 (s),1627 (w), 1491 (m), 1451 (w), 1384 (w), 1372 (w), 1293 (w), 1247 (s),1139 (m), 1119(m), 958 (w), 906 (w), 837 (m). ¹H NMR (400 MHz, CDCl₃):87.30 (d, J=2.4 Hz, 4H, aromatic CH), 7.02 (d, J=6.4 Hz, 4H, aromaticCH), 7.02 (dd, J=19.8, 9.4 Hz, 4H, ArCHCH₂), 6.79 (d, J=8.8 Hz, 4H,aromatic CH), 5.71 (dd, J=17.8, 1.6 Hz, 4H, ArCHCH₂), 5.21 (dd, J=11.4,1.6 Hz, 4H, ArCHCH₂), 4.48 (septet, J=6.2 Hz, 4H, (CH₃)₂CHOAr), 4.01 (t,J=7.0 Hz, 8H, CO₂CH₂), 2.88 (t, J7.8 Hz, 8H, ArCH₂CH₂CO₂), 2.59 (t,J=7.8 Hz, 8H, ArCH₂CH₂CO₂), 1.58 (m, 8H, CO₂CH₂CH₂CH₂Si(Me)₂), 1.36-1.25(m, 8H, SiCH₂CH₂CH₂Si(Me)₂), 1.33 (d, J=5.6 Hz, 24H, (CH₃)₂CHOAr),0.58-0.52 (m, 16H, CH₂Si(Me)₂CH₂), 0.47-0.42 (m, 8H, Si(CH₂)₄), −0.04(s, 24H, Si(Me)₂). ¹³C NMR (100 MHz, CDCl₃): δ 172.77, 153.44, 132.40,131.76, 128.30, 127.61, 126.14, 114.30, 113.78, 70.96, 67.16, 36.30,30.38, 23.33, 22.33, 20.20, 18.65, 17.63, 11.30, −3.26. LRMS Calcd forC₈₈H₁₄₀O₁₂Si₅K (M+K): 1569.9. Found: 1569.5. Anal. Calcd forC₈₈H₁₄₀O₁₂Si₅: C, 69.06; H, 9.22. Found: C, 69.31; H, 9.36.

Example 14

Synthesis of [(PCy₃)CI₂Ru═CH-o-O-i-PrC₆H₃(CH₂)₂C00(CH₂)₃Si(Me)₂CH₂₃Si]₄(Formula 30). (PCy₃)₂Cl₂Ru═CHPh (2) (792 mg, 0.962 mmol, 4.3 equiv) andCuCl (106 mg, 1.07 mmol, 4.8 equiv) were added to a 25 mL round-bottomflask and suspended in 12 mL of CH₂Cl₂. Dendrimer 29 (341 mg, 0.223mmol, 1.0 equiv) was added to this mixture through a cannula in 10 mL ofCH₂Cl₂. The mixture was stirred for a period of 3 h at 22° C., duringwhich time the original purple solution turned dark brown in color. Thefollowing work-up procedures were conducted in air with reagent-gradesolvents. The mixture was concentrated at reduced pressure and passedthrough a short plug of silica gel in 3:2 hexanes:Et₂O (brown bandrapidly elutes). Product fractions were pooled and concentrated. Thismaterial was passed through a second column of silica gel, this timewith a gradient elution (1:1 hexanes:CH₂Cl₂to 2:3 hexanes:CH₂Cl₂ to 1:3hexanes:CH₂Cl₂ to 100% CH₂Cl₂). Finally, the column was flushed withEt₂O, at which point the product elutes (brown band). Solvent removalafforded a dark brown crystalline solid (637 mg, 0.194 mmol, 87%). IR(NaCl): 2927 (s), 2852 (s), 1955 (w), 1733 (s), 1684 (w), 1610 (w), 1582(w), 1488 (m), 1447 (m), 1417 (w), 1385 (m), 1296 (w), 1247 (m), 1222(m), 1204 (m), 1134 (m), 1104 (m), 913 (w), 891 (w), 849 (m), 774 (w),735 (m), 702 (w). ¹H NMR (400 MHz, CDCl₃): 6 17.38 (d, J=4.0 Hz, 4H,Ru═CHAr), 7.52 (s, 4H, aromatic CH), 7.46 (d, J=8.8 Hz, 4H, aromaticCH), 6.98 (d, J=8.8 Hz, 4H, aromatic CH), 5.23 (septet, J=6.2 Hz, 4H,(CH₃)₂CHOAr), 4.03 (t, J=7.1 Hz, 8H, CO₂CH₂), 3.03 (t, J=7.7 Hz, 8H,ArCH₂CH₂CO₂), 2.64 (t, J=7.7 Hz, 8H, ArCH₂CH₂CO₂) 2.32 (m, 12H, PCH),2.20-1.20 (m, 136H, CO₂CH₂CH₂CH₂Si(Me)₂, SiCH₂CH₂CH₂Si(Me)₂, andP(CH(CH₂)₅)₃), 179 (d, J=6.2 Hz, 24H, (CH₃)₂CHOAr), 0.60-0.52 (m, 16H,CH₂Si(Me)₂CH₂), 0.50-0.45 (m, 8H, Si(CH₂)₄), −0.03 (s, 24H, Si(Me)₂).¹³C NMR (100 MHz, CDCl₃): δ 279.24, 172.60, 151.29, 143.79, 134.69,129.42, 122.51 (d, J_(OC)=5.9 Hz), 113.19, 75.50 (d, J_(OC)=7.8 Hz),67.27, 36.36, 35.67 (d, J_(PH)=24.4 Hz), 30.14, 29.73, 27.80 (d,J_(PH)=10.7 Hz), 26.33, 23.26, 22.14, 20.14, 18.58, 17.56, 11.26, −3.33.³¹P NMR (162 MHz, CDCl₃): δ59.17 (s, PCy₃). LRMS Calcd forC₁₅₆H₂₆₄Cl₈O₁₂P₄Ru₄Si₅Na₂(M+2Na)+: 3331.2. Found: 3331.8. Anal. Calcdfor C₁₅₆H₂₆₄Cl₈O₁₂P₄Ru₄Si₅: C, 57.05; H, 8.10. Found: C, 56.80; H, 8.00.

Example 15

Synthesis of [(4,5-dihydrolMES)Cl₂Ru═CH-o-O-i-PrC₆H₃(CH₂)₂C00(CH₂)₃Si(Me)₂(CH₂)₃Si]₄(formula 31). Theunmetallated dendrimer (29) (227 mg, 0.148 mmol, 1.0 equiv) was weighedinto a 25 mL round-bottom flask and dissolved in 15 mL of CH₂Cl₂.(4,5-dihydrolMES)(PCy₃)Cl₂Ru═CHPh (3) (606 mg, 0.714 mmol, 4.8 equiv)and CuCl (72.0 mg, 0.731 mmol, 4.9 equiv) were added directly to thissolution as solids. The mixture was stirred for 2 h at 22° C., duringwhich time the original purple solution turned a dark green/brown color.The following work-up procedures were conducted in air using reagentgrade solvents. The mixture was concentrated at reduced pressure andpassed through a short column of silica gel using a gradient elution(100% CH₂Cl₂ to 4:1 hexanes:Et₂O to 1:1 hexanes:Et₂O to 100% Et₂O). Thegreen band was collected and concentrated, affording a greenmicrocrystalline solid (277 mg, 0.08 16 mmol, 55%). IR (NaCl): 3432 (b),2915 (m), 1732 (s), 1632 (w), 1607 (w), 1595 (w), 1487 (s), 1418 (m),1259 (s), 1221 (m), 1132 (m), 1104 (m), 1034 (w), 912 (w), 849 (w), 579(w). ¹H NMR (300 MHz, CDCl₃): δ 16.51 (s, 4H, Ru═CHAr), 7.33 (d, J=7.0Hz, 4H, aromatic CH), 7.07 (s, 16H, mesityl aromatic CH), 6.74-6.66 (m,8H, aromatic CH), 4.85 (septet, J=6.3 Hz, 4H, (CH₃)₂CHOAr), 4.17 (s,16H, N(CH₂)₂N), 4.02 (t, J=7.0 Hz, 8H, CO₂CH₂), 2.91 (t, J=7.8 Hz, 8H,ArCH₂CH₂CO₂), 2.53 (t, J=7.8 Hz, 8H, ArCH₂CH₂CO₂), 2.47 (s, 48H, mesitylo-CH₃), 2.41 (s, 24H, mesitylpCH₃), 1.61 (m, 8H, CO₂CH₂CH₂CH₂Si(Me)₂),1.40-1.25 (m, 8H, SiCH₂CH₂CH₂Si(Me)₂), 1.24 (d, J=6.3 Hz, 24H,(CH₃)₂CHOAr), 0.61-0.45 (m, 24H, CH₂Si(Me)₂CH₂ and Si(CH₂)₄), −0.02 (s,24H, Si(Me)₂). ¹³C NMR. (75 MHz, CDCl₃): δ 297.07 (d, J=166.0 Hz),211.32, 172.81, 150.80, 145.16, 138.76, 134.28, 130.42, 130.29, 129.80,129.39, 128.74, 128.22, 74.41, 67.19, 51.44, 36.03, 29.54, 23.14, 21.53,20.96, 20.60, 20.03, 18.48, 17.47, 11.12, −4.13. LRMS Calcd forC₁₆₈H₂₄₀Cl₈N₈O₁₂Ru₄Si₅(M+4H): 3393.1. Found: 3393.1. Anal. Calcd forC₁₆₈H₂₃₆Cl₈N₈O₁₂Ru₄Si₅: C, 59.56; H, 7.02. Found: C, 59.55; H, 6.96.

Example 16

Representative Experimental Procedure for RCM Catalyzed by Monomer (4,5dihydrolMES)Cl₂Ru═CH-o-0-PrC₆H₄ (formula 5). Triene (7) (50.1 mg, 0.329mmol, 1.0 equiv) was weighed out in a 25 mL round-bottom flask anddissolved in 3 mL of CH₂Cl₂ (0.1 M).(4,5-dihydrolMES)Cl₂RuCH-o-O-i-PrC₆H₄ (5) (9.80 mg, 0.0156 mmol, 0.0474equiv) was added as a solid and the resulting deep green solution wasstirred at 22° C. TLC analysis after 10 mm indicated completion of thereaction. As usual, work-up procedures were conducted in air usingreagent-grade solvents. The mixture was concentrated at reduced pressureand passed through a short column of silica gel in 2:1 hexanes:CH₂Cl₂affording diene (8) (33.4 mg, 0.269 mmol, 82%) as a colorless oil (TLCR_(f)=0.46 in 9:1 hexanes:Et₂O). The catalyst was then retrieved as agreen solid by flushing the silica column with 100% CH₂Cl₂ (9.60 mg,0.0153 mmol, 98%).

Example 17

Representative Experimental Procedure for RCM Catalyzed by Dendritic[(PCY₃)Cl₂Ru═CH-o-0-i-PrC₆H₃(CH₂)₂C00(CH₂)₃Si(Me)₂(CH₂)₃Si]₄ (formula30). Tosyl amide (32) (250 mg, 0.995 mmol, 1.0 equiv) and dendriticcatalyst (30) (43.9 mg, 0.0140 mmol, 0.014 equiv) were weighed into a 50mL round-bottom flask. The flask was equipped with a reflux condenser,evacuated, and filled with an atmosphere of argon. The vessel wascharged with CH₂Cl₂(20 mL, 0.05 M) and submerged into an oil bathpreheated to 45° C. The reaction was stirred for 15 minutes, at whichpoint TLC analysis indicated completion of the reaction. Removal of thesolvent in vacuo afforded a dark brown oil that was purified by silicagel chromatography (100% CH₂Cl₂), affording 33 as a white solid (219 mg,0.983 mmol, 99%). The column was then flushed with 100% Et₂O to recoverthe dendritic catalyst as a brown solid residue (46.2 mg, 0.0141 mmol,100%). The recovered catalyst was transferred directly into a new flaskfor a subsequent reaction. As discussed above, Ru recovery on thedendrimer could be quickly analyzed upon inspection of the ¹H NMR (400MHz) spectrum. Integration of the benzylic methylene protons at 3.03 ppm(metal-occupied sites) and 2.88 ppm (metal-vacant sites) provided aratio of 88:12 respectively.

Example 18

Experimental Procedure for RCM Catalyzed by Dendritic[(4,5-dihydrolMES)Cl₂Ru═CH-o-O-i-PrC₆H₃(CH₂)₂COO(CH₂)₃5i(Me)₂(CH₂)₃Si]₄(formula 31). Diene (11) (32.7 mg, 0.233 mmol, 1.0 equiv) was weighedinto a 25 mL round-bottom flask and dissolved in 5 mL of CH₂Cl₂ (0.05M). Dendritic catalyst 31 (12.4 mg, 0.00366 mmol, 0.016 equiv) was addedas a solid and the solution was allowed to stir at 22° C. TLC analysisafter 2 h indicated completion of the reaction. Work-up proceduresproceeded in air with reagent-grade solvents. The mixture wasconcentrated at reduced pressure and passed through a short plug ofsilica gel in 100% CH₂Cl₂, affording (12) (20.4 mg, 0.1819 mmol, 78%) asa colorless oil (TLC R_(f)=0.25 in 4:1 hexanes:Et₂O). The catalyst wasthen flushed off of the column with 100% Et₂O affording 12.3 mg (0.00363mmol, 99%) of a green solid. Ru recovery on the dendrimer was assessedusing ¹H NMR spectroscopy (400 MHz). Integration of the isopropoxymethine proton for both metal-occupied (4.90 ppm) and metal-vacant (5.71ppm) sites gave a ratio of 92:8 respectively, indicative of 8% metalloss.

Example 19

Synthesis of an Immobilized Catalyst. This procedure allows installmentof the linker and the active metal complex in a single step. Treatmentof the compound 35 with a stoichiometric amount of(4,5-dihydroIMES)(PCy₃) Cl₂Ru═CHPh in the presence ofallylchlorodimethylsilane led to successful ring-opening crossmetathesis and metallation of the styrenyl ether “docking site.”Subsequent diffusion of this product into the pores of a sol gel sample(200 A° pore size glass monoliths, available from Geltech, Orlando,Fla.) resulted in a substitution reaction involving the labile Si—Clbond with the free hydroxyl groups on the glass surface. After extensivewashing and drying in vacuo, a bright green glass pellet (Formula 6) wasrecovered which showed good activity in the RCM of the terminal diene 44(0.10 mmol scale) to yield 45 (as shown in Scheme 7). The immobilizedcatalyst was then carried through three iterative rounds of metathesisto covert diene 44 to the cyclic compound 45 as shown below.

Although successive ring-closures required longer reaction times, >90%conversion was observed in each case, the following factors wereobserved: (1) Derivatization of the sol gel pellet resulted in a 1.0 mgincrease in mass. Calculations therefore suggest that the RCM ofcompound 7 was mediated by a very small amount of active catalyst (˜1mol %). This may partly account for the slow reaction rate, particularlyin the second and third cycles. Increasing the catalyst loading to 5 mol% will lead to dramatic improvements in reaction rate. (2) In contrastto reactions run with 5 mol % Formula 1 or 5, the spectrum of theunpurified reaction mixture consisted of >98% pure cycloolefin (nocatalyst or byproduct thereof could be detected). (3) No filtration stepwas required to isolate the product. The reaction mixture was simplyremoved with a Pasteur pipette, the glass sample was washed with CH₂Cl₂,and fresh substrate was added.

Although the invention has been described in detail for the purpose ofillustration, it is understood that such detail is solely for thispurpose, and variations can be made therein by those skilled in the artwithout departing from the spirit and scope of the invention asdescribed by the appended claims.

1. A transition metal catalyst comprising: a substrate having at leastone functional group; a transition metal having at least one substituentthat reacts with at least one functional group on the substrate tochemically bond the transition metal to the substrate, the transitionmetal selected from the group consisting of ruthenium, osmium andtungsten.
 2. The transition metal catalyst of claim 1 wherein thesubstituent is selected from the group consisting of alkyl halosilanes,akenyl halosilanes, alkoxy halosilanes, aryloxy halosilanes, arylhalosilanes, alkyl halides, cycloalkyl halides, alkenyl halides,cycloalkenyl halides, aromatic and heteroaromatic halides, acidchlorides, anhydrides, succimidyl esters, epoxides, thiols, acrylate,methacrylate, acrylamide, methacrylamide, benzophenone, and derivativesthereof.
 3. The transition metal catalyst of claim 1 wherein thesubstituent is alkylldimethylsilylcholride.
 4. The transition metalcatalyst of claim 1 wherein the substrate is a porous or a non-poroussolid phase.
 5. The transition metal catalyst of claim 1 wherein thesubstrate is selected from the group consisting of glasses, metals,non-metals, ceramics, rubbers and polymeric materials.
 6. The transitionmetal catalyst of claim 1 wherein the substrate is part of a containingvessel.
 7. A composition comprising a transition metal catalyst havingthe following structure:

wherein A is a polyvalent atom selected from the group consisting ofcarbon, nitrogen, silicon and phosphorous; wherein R₅, R₆, R₇ and R₈each comprises the following structure:

wherein: M comprises a transition metal; X comprises oxygen, sulfur,nitrogen or phosphorus; R comprises an alkyl, alkenyl, alkynyl, aryl,alkoxy, alkenyloxy, alkynyloxy, aryloxy, alkoxy carbonyl, alkylamino,alkylthio, alkylsulfonyl, or alkylsulfinyl; each optionally substitutedwith an alkyl, halogen, aryl or heteroaryl moiety; R₁ and R₂ eachcomprises, or together comprise, an electron withdrawing group; and Zcomprises an electron-donating heterocyclic carbene ligand or aphosphine group.
 8. The composition of claim 7 wherein A is silicon. 9.The composition of claim 7 wherein M is a transition metal selected fromthe group consisting of ruthenium, osmium and tungsten.
 10. Thecomposition of claim 7 wherein M is ruthenium.
 11. The composition ofclaim 7 wherein X is oxygen.
 12. The composition of claim 7 wherein R isa lower alkyl group.
 13. The composition of claim 7 wherein R isisopropyl.
 14. The composition of claim 7 wherein each of R₁ and R₂ is ahalogen.
 15. The composition of claim 7 wherein each of R₁ and R₂ ischlorine.
 16. The composition of claim 7 wherein Z comprises a phosphinemoiety having the formula P(Cy)₃.
 17. The composition of claim 7 whereinZ comprises an aromatic ring structure having the following structure:

wherein R₃ and R₄ each comprises an aromatic ring moiety.
 18. A methodof immobilizing a transition metal catalyst comprising: reacting thetransition metal catalyst with a chemical coupling agent to form anadduct with the transition metal catalyst; and contacting the adductwith a substrate to chemically bond the adduct with the substratethrough covalent chemical bonding, ionic bonding, non-ionic interaction,or combinations thereof.
 19. The method of claim 18 further comprisingreacting the transition metal catalyst with a chemical coupling agentthat is chemically bonded to the substrate.
 20. The method of claim 18wherein the chemical coupling agent comprises at least one compoundselected from the group consisting of alkyl halosilanes, akenylhalosilanes, alkoxy halosilanes, aryloxy halosilanes and arylhalosilanes, alkyl and cycloalkyl halides, alkenyl and cycloalkenylhalides, aromatic and heteroaromatic halides, acid chlorides,anhydrides, succimidyl esters, epoxides and thiols.
 21. The method ofclaim 18 wherein the chemical coupling agent isallylchlorodimethylsilane.
 22. The method of claim 18 wherein thesubstrate is selected from the group consisting of glasses, metals,non-metals, ceramics, rubbers and polymeric materials.
 23. The method ofclaim 18 wherein the substrate is a porous or non-porous material. 24.The method of claim 18 wherein the substrate is a porous sol-gel.